12-phase flow (10)

1. 1FRAME
   Peri-infusion cardiotoxicity = symptom onset within minutes-hours of biologic / CAR-T / blood / contrast infusion. Four phenotypes: mAb infusion reaction, CAR-T CRS, transfusion reaction (TRALI / TACO / hemolytic / anaphylactic), contrast reaction. CRITICAL FIRST STEP: STOP THE INFUSION immediately + maintain IV access. Cause-specific antidote: tocilizumab for CRS; epinephrine for anaphylaxis; diuretic for TACO; ventilatory support for TRALI; supportive for mAb infusion reaction.
   inputs: specific_infusion_agent_and_premedication_status, temporal_correlation_minutes_to_hours_from_infusion_start
   advance: peri-infusion timing + agent + symptom complex framed
2. 2ENTRY
   STOP infusion immediately + maintain IV access; rapid response activation; oxygen + IV fluids cautious; activate cardiology + allergy/immunology + oncology / blood-bank as appropriate; bedside ECG + echo + troponin
   inputs: age, underlying_diagnosis_and_indication_for_infusion, symptoms_complex_dyspnea_chest_pain_rash_hypotension_fever
   advance: infusion stopped + multidisciplinary team activated
3. 3CONTEXT
   Underlying diagnosis + indication + specific agent + premedication status + prior reaction history + chronic HF/renal status (TACO risk amplifier) + cycle # (first dose dominant for mAb)
   inputs: prior_infusion_reactions_or_allergies, underlying_chronic_hf_or_renal_failure, creatinine_serial
   advance: patient + agent context complete
4. 4RED_FLAGS
   Anaphylactic shock (epinephrine NOW); CAR-T CRS grade 3-4 with cardiotoxicity (tocilizumab + ICU); TRALI with hypoxia + bilateral infiltrates (intubation imminent); cardiogenic shock (norepinephrine + MCS consideration); arrhythmia storm (CRS-mediated VT/VF); refractory hypotension despite 1-2 L IVF
   inputs: sbp, spo2_and_respiratory_rate, lactate
   actions: cardiogenic_shock
   advance: red flags screened + cause-specific antidote initiated
5. 5INITIAL_WORKUP
   Troponin (presentation + 6h + 24h), NT-proBNP, BMP, CBC with diff, lactate, LFTs, coags, ABG, tryptase if anaphylaxis suspected (window 1-3h), IL-6 and cytokine panel if CRS suspected, LDH + haptoglobin + smear if hemolytic transfusion reaction suspected, ECG, bedside echo with strain, CXR (TRALI vs TACO pattern), urine output
   inputs: troponin_serial_at_presentation_6h_24h, nt_probnp, ecg_with_arrhythmia_screen, echo_with_lvef_and_strain, cxr_for_pulmonary_infiltrates_volume_status, lactate
   actions: acute_pulm_edema, panel.cardiac, panel.renal
   advance: workup documented + reaction phenotype characterized
6. 6BRANCHING_WORKUP
   CRS grade ≥2 with cardiotoxicity → tocilizumab + steroid + ICU; anaphylaxis confirmed → epinephrine + airway + ICU if shock; TACO confirmed → diuretic + slow re-transfusion plan + IV iron alternative; TRALI confirmed → supportive ventilation + AABB notification + donor exclusion; hemolytic reaction → check ABO/Rh + Coombs + transfusion service investigation
   inputs: tryptase_if_anaphylaxis_suspected, il_6_and_cytokine_panel_if_crs_suspected, cbc_with_diff_ldh_haptoglobin_if_hemolytic_reaction_suspected
   actions: acs_pathway
   advance: cause-specific pathway identified + antidote initiated
7. 7TREATMENT
   STOP THE INFUSION (cornerstone; covers all 4 phenotypes). CAUSE-SPECIFIC: (1) CAR-T CRS grade ≥2 with cardiotoxicity → tocilizumab 8 mg/kg IV (max 800 mg) ± dexamethasone 10-20 mg IV q6h (siltuximab as alternative anti-IL-6); (2) anaphylaxis → epinephrine 0.3 mg IM (1:1000) repeat q5-15 min + H1 (diphenhydramine 25-50 mg IV) + H2 (famotidine 20 mg IV) + methylprednisolone 125 mg IV + IV crystalloid 1-2 L bolus; (3) TACO → furosemide 40-80 mg IV bolus + slow further transfusion + IV iron alternative if iron-deficient (ferric carboxymaltose); (4) TRALI → respiratory support (HFNC → NIV → intubation per severity); diuretic NOT helpful; AABB notification + donor exclusion. STANDARD: norepinephrine for refractory shock; oxygen to SpO2 ≥92%; lung-protective ventilation. GDMT initiated once stable + LVEF reduced (post-CRS-CMP often reversible — consider 4-pillar GDMT bridge).
   inputs: sbp
   actions: protocol.cardiogenic_shock
   advance: cause-specific antidote + supportive bundle delivered
8. 8DISPOSITION
   CICU for cardiogenic shock or refractory CRS; ICU for anaphylactic shock or TRALI; cardiology floor only if mild and resolving; allergy/immunology + oncology + blood bank co-management
   advance: unit assigned + multidisciplinary plan documented
9. 9MONITORING
   Continuous telemetry + arterial line if shock; serial troponin q6h × 24h; daily NT-proBNP; daily echo with strain × 48h; daily BMP + LFTs (CRS hepatotoxicity); cytokine trend if tocilizumab given; respiratory monitoring (TRALI / TACO); blood-bank investigation results; allergy/immunology written report for chart
   inputs: troponin_serial_at_presentation_6h_24h, nt_probnp
   actions: panel.cardiac
   advance: monitoring + multidisciplinary surveillance documented
10. 10FOLLOWUP
    Cardio-oncology / cardiology follow-up at 2 wks + 6 wks + 3 mo with echo (LVEF reversibility for CRS-CMP); allergy/immunology consult for premedication protocol + future infusion guidance + alternative agent recommendation; for transfusion reactions: blood-bank donor exclusion + future transfusion strategy (washed RBC, male-only plasma); for repeat CAR-T → CRS prophylaxis with pre-emptive tocilizumab in high-risk; iron-deficiency anemia switch to slow IV iron formulations (ferric carboxymaltose / ferric derisomaltose); patient + family education on early reaction recognition
    advance: cardio-oncology + allergy/immunology + blood-bank pathway booked